口腔粘膜下纤维化及其癌变组织中细胞凋亡及Bcl-2、Bax的表达研究
摘要
目的:通过检测口腔粘膜下纤维化(oral submucous fibrosis,OSF)及其癌变组织中的细胞凋亡状况以及Bcl-2、Bax表达和分布的差异,进一步探讨OSF的发病机制。
方法:取10例健康志愿者的颊部粘膜、45例OSF(早、中、晚期各15例)和10例OSF癌变患者的新鲜病变组织,常规石蜡包埋。通过TUNEL测定法检测组织上皮中凋亡细胞的数量,并进一步采用免疫组织化学SABC法分别检测Bcl-2和Bax的表达和分布的差异。凋亡细胞数量用凋亡指数AI(apoptotic index)表示,Bcl-2及Bax蛋白的染色强度用染色得分来评价。
结果:1.OSF晚期、癌变组织中的AI与各组比较差别均具有显著性意义(P＜0.05),其中癌变组织AI高于OSF晚期(P＜0.05);OSF早、中期与正常对照组AI相互比较差别无显著性意义(P＞0.05)。
2.Bcl-2蛋白在正常口腔粘膜上皮中为阴性或非常弱的表达,在OSF早期表达增高,并随病变发展表达逐渐增强。OSF癌变组与正常对照组、OSF早、中期有显著性差异(P＜0.05),但与OSF晚期组比较差别无显著性意义(P＞0.05);OSF晚期组与正常对照组差别有显著性意义(P＜0.05);OSF早、中期与正常对照组比较差别无显著意义(P＞0.05)。
3.Bax蛋白在正常口腔粘膜上皮全层可见弱的表达,在OSF早期下降,自中期开始表达逐渐升高。OSF癌变组与OSF早、中期差别有显著性意义(P＜0.05),但与OSF晚期比较差别无显著性意义(P＞0.05);OSF晚期组与OSF早期差别有显著性意义(P＜0.05);OSF早、中期组及正常对照组之间比较差别无显著性意义(P＞0.05)。
2.Bcl-2蛋白在OSF癌变组织中的阳性表达率明显升高,推测该蛋白通过抑制细胞凋亡,在OSF癌变中发挥着重要作用。
3.Bax在OSF晚期细胞凋亡中发挥重要作用,并与OSF癌变细胞凋亡有关。
Objective: To investigate the apoptosis and the expression of apoptosis-associated proteins Bcl-2 and Bax in oral submucous fibrosis and cancerization of oral submucous fibrosis, so as to discuss the pathological mechanism of OSF.
Methods: The apoptosis and the expression of Bcl-2 and Bax were obsevered in 45 cases of OSF, 10 cases of cancerization of OSF and 10 cases of normal oral mucosa by TUNEL and immunohistochemistry. The percentage of apoptotic cells labeled by the TUNEL method was estimated as an apoptotic index(AI). The rate of positive reaction were observed and counted blindly,and the staining intensity were judged by staining score.
Results: 1. TUNEL was positive in normal oral mucosa,the positive staining could been mostly seen in stratum granulosum and strayum spinosum. The AI was significant increased in cancerization of OSF,the differences between cancerization of OSF and all stages of OSF and normal oral mucosa was significant(P<0.05). No significant differences was found in AI between early, medium-term stages of OSF and normal oral mucosa(P>0.05).
2. Bcl-2 protein was detected negative or weakly positive in normal oral mucosa, which confined to basal membrane, but a upgrade increase of expression could be found in early stage of OSF, and enhanced with the aggravation of pathological grades. The expression in cancerization of OSF was higher than early, medium-term stages of OSF and normal oral mucosa(P<0.05),but no significant differences was found with advanced stage of OSF. No statistically significant differences were found between normal oral mucosa and early,medium-term stage of OSF(P>0.05).
3. Bax immunostaining was seen slight throughout the thickness of the normal oral mucosa, but Bax expression was declined in early stage of OSF. The differences between early,medium-term stages of OSF and cancerization of OSF was statistically significant (P<0.05). The expression of Bax increased at advanced stage of OSF compared with early and medium-term stages of OSF(P<0.05).No significant differences were found between normal oral mucosa and early and medium-term stages of OSF(P>0.05).
Conclusions: 1. Apoptotic cell death in epithelium was increased at advanced stage of OSF, indicates excessive apoptosis occurs may contribute to epithelial atrophy.
2. The upgrade expression of Bcl-2 protein in cancerization of OSF, it was supposed that may act as an important role in the cancerization of OSF by allowing escape from apoptosis.
3. Overexpression of Bax was contributed to the apoptosis in advanced stage of OSF, and related to the apoptosis in cancerization of OSF.
方法:取10例健康志愿者的颊部粘膜、45例OSF(早、中、晚期各15例)和10例OSF癌变患者的新鲜病变组织,常规石蜡包埋。通过TUNEL测定法检测组织上皮中凋亡细胞的数量,并进一步采用免疫组织化学SABC法分别检测Bcl-2和Bax的表达和分布的差异。凋亡细胞数量用凋亡指数AI(apoptotic index)表示,Bcl-2及Bax蛋白的染色强度用染色得分来评价。
结果:1.OSF晚期、癌变组织中的AI与各组比较差别均具有显著性意义(P＜0.05),其中癌变组织AI高于OSF晚期(P＜0.05);OSF早、中期与正常对照组AI相互比较差别无显著性意义(P＞0.05)。
2.Bcl-2蛋白在正常口腔粘膜上皮中为阴性或非常弱的表达,在OSF早期表达增高,并随病变发展表达逐渐增强。OSF癌变组与正常对照组、OSF早、中期有显著性差异(P＜0.05),但与OSF晚期组比较差别无显著性意义(P＞0.05);OSF晚期组与正常对照组差别有显著性意义(P＜0.05);OSF早、中期与正常对照组比较差别无显著意义(P＞0.05)。
3.Bax蛋白在正常口腔粘膜上皮全层可见弱的表达,在OSF早期下降,自中期开始表达逐渐升高。OSF癌变组与OSF早、中期差别有显著性意义(P＜0.05),但与OSF晚期比较差别无显著性意义(P＞0.05);OSF晚期组与OSF早期差别有显著性意义(P＜0.05);OSF早、中期组及正常对照组之间比较差别无显著性意义(P＞0.05)。
2.Bcl-2蛋白在OSF癌变组织中的阳性表达率明显升高,推测该蛋白通过抑制细胞凋亡,在OSF癌变中发挥着重要作用。
3.Bax在OSF晚期细胞凋亡中发挥重要作用,并与OSF癌变细胞凋亡有关。
Objective: To investigate the apoptosis and the expression of apoptosis-associated proteins Bcl-2 and Bax in oral submucous fibrosis and cancerization of oral submucous fibrosis, so as to discuss the pathological mechanism of OSF.
Methods: The apoptosis and the expression of Bcl-2 and Bax were obsevered in 45 cases of OSF, 10 cases of cancerization of OSF and 10 cases of normal oral mucosa by TUNEL and immunohistochemistry. The percentage of apoptotic cells labeled by the TUNEL method was estimated as an apoptotic index(AI). The rate of positive reaction were observed and counted blindly,and the staining intensity were judged by staining score.
Results: 1. TUNEL was positive in normal oral mucosa,the positive staining could been mostly seen in stratum granulosum and strayum spinosum. The AI was significant increased in cancerization of OSF,the differences between cancerization of OSF and all stages of OSF and normal oral mucosa was significant(P<0.05). No significant differences was found in AI between early, medium-term stages of OSF and normal oral mucosa(P>0.05).
2. Bcl-2 protein was detected negative or weakly positive in normal oral mucosa, which confined to basal membrane, but a upgrade increase of expression could be found in early stage of OSF, and enhanced with the aggravation of pathological grades. The expression in cancerization of OSF was higher than early, medium-term stages of OSF and normal oral mucosa(P<0.05),but no significant differences was found with advanced stage of OSF. No statistically significant differences were found between normal oral mucosa and early,medium-term stage of OSF(P>0.05).
3. Bax immunostaining was seen slight throughout the thickness of the normal oral mucosa, but Bax expression was declined in early stage of OSF. The differences between early,medium-term stages of OSF and cancerization of OSF was statistically significant (P<0.05). The expression of Bax increased at advanced stage of OSF compared with early and medium-term stages of OSF(P<0.05).No significant differences were found between normal oral mucosa and early and medium-term stages of OSF(P>0.05).
Conclusions: 1. Apoptotic cell death in epithelium was increased at advanced stage of OSF, indicates excessive apoptosis occurs may contribute to epithelial atrophy.
2. The upgrade expression of Bcl-2 protein in cancerization of OSF, it was supposed that may act as an important role in the cancerization of OSF by allowing escape from apoptosis.
3. Overexpression of Bax was contributed to the apoptosis in advanced stage of OSF, and related to the apoptosis in cancerization of OSF.
引文
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